Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes

Cutaneous lupus erythematosus (CLE) is a common manifestation of systemic lupus erythematosus (SLE), and CLE can also develop without systemic involvement. CLE can be difficult to treat and negatively contributes to quality of life. Despite the importance of CLE, our knowledge of what differentiates cutaneous lupus subtypes is limited. Here, we utilized a large cohort of 90 CLE lesional biopsies to compare discoid lupus erythematosus (DLE) and subacute cutaneous lupus (SCLE) in patients with and without associated SLE in order to discern the drivers of disease activity and possibly uncover better treatment targets. Overall, we found that DLE and SCLE share many differentially expressed genes (DEG) reflecting type I interferon (IFN) signaling and repression of EGFR pathways. No differences between CLE only and SLE-associated CLE lesions were found. Of note, DLE uniquely expresses an IFN-γ node. Unbiased cluster analysis of the DEGs identified two groups separated by neutrophilic vs. monocytic signatures that did not sort the patients based on clinical phenotype or disease activity. This suggests that unbiased analysis of the pathobiology of CLE lesions may be important for personalized medicine and targeted therapeutic decision making.

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B Cell Signatures Distinguish Cutaneous Lupus Erythematosus Subtypes and the Presence of Systemic Disease Activity

Frontiers in Immunology ◽

10.3389/fimmu.2021.775353 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lisa Abernathy-Close ◽

Stephanie Lazar ◽

Jasmine Stannard ◽

Lam C. Tsoi ◽

Sean Eddy ◽

...

Keyword(s):

Disease Activity ◽

B Cell ◽

Lupus Erythematosus ◽

Systemic Disease ◽

Cutaneous Lupus Erythematosus ◽

Discoid Lupus Erythematosus ◽

Type I ◽

Systemic Lupus ◽

Cutaneous Inflammation ◽

Cutaneous Lupus

Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease characterized by a diverse cadre of clinical presentations. CLE commonly occurs in patients with systemic lupus erythematosus (SLE), and CLE can also develop in the absence of systemic disease. Although CLE is a complex and heterogeneous disease, several studies have identified common signaling pathways, including those of type I interferons (IFNs), that play a key role in driving cutaneous inflammation across all CLE subsets. However, discriminating factors that drive different phenotypes of skin lesions remain to be determined. Thus, we sought to understand the skin-associated cellular and transcriptional differences in CLE subsets and how the different types of cutaneous inflammation relate to the presence of systemic lupus disease. In this study, we utilized two distinct cohorts comprising a total of 150 CLE lesional biopsies to compare discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus (ACLE) in patients with and without associated SLE. Using an unbiased approach, we demonstrated a CLE subtype-dependent gradient of B cell enrichment in the skin, with DLE lesions harboring a more dominant skin B cell transcriptional signature and enrichment of B cells on immunostaining compared to ACLE and SCLE. Additionally, we observed a significant increase in B cell signatures in the lesional skin from patients with isolated CLE compared with similar lesions from patients with systemic lupus. This trend was driven primarily by differences in the DLE subgroup. Our work thus shows that skin-associated B cell responses distinguish CLE subtypes in patients with and without associated SLE, suggesting that B cell function in skin may be an important link between cutaneous lupus and systemic disease activity.

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Evaluating change in disease activity needed to reflect meaningful improvement in quality of life for clinical trials in cutaneous lupus erythematosus

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2020.07.047 ◽

2020 ◽

Author(s):

Srita Chakka ◽

Rebecca L. Krain ◽

Sarah Ahmed ◽

Josef Symon S. Concha ◽

Rui Feng ◽

...

Keyword(s):

Quality Of Life ◽

Clinical Trials ◽

Disease Activity ◽

Lupus Erythematosus ◽

Cutaneous Lupus Erythematosus ◽

Meaningful Improvement ◽

Cutaneous Lupus

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Factors associated with quality of life in cutaneous lupus erythematosus using the Revised Wilson and Cleary Model

Lupus ◽

10.1177/0961203320951842 ◽

2020 ◽

Vol 29 (13) ◽

pp. 1691-1703 ◽

Cited By ~ 1

Author(s):

Motolani E Ogunsanya ◽

Sung Kyung Cho ◽

Andrew Hudson ◽

Benjamin F Chong

Keyword(s):

Quality Of Life ◽

Body Image ◽

Side Effects ◽

Disease Activity ◽

Lupus Erythematosus ◽

Cutaneous Lupus Erythematosus ◽

Factors Associated ◽

The Impact ◽

Cutaneous Lupus

Objectives The purpose of this study was to characterize the impact of cutaneous lupus erythematosus (CLE) in adults and identify the clinical and non-clinical factors associated with quality of life (QoL), using the Revised Wilson and Cleary Model. Methods 101 patients diagnosed with CLE were included in this cross-sectional study. QoL was measured with the Cutaneous Lupus Erythematosus Quality of Life (CLEQoL) scale and disease activity and damage with the Cutaneous Lupus Activity and Severity Index (CLASI). Patient demographics, clinical, and disease characteristics were also collected. Descriptive statistics were calculated, and multiple regression was employed to determine significant (p < 0.05) predictors of overall QoL. Data were analyzed using SPSS v24. Results The overall regression QoL model was significantly different from zero, (F = 24.96; df = 14, 76; p = <0.001). Disease activity (β = 0.13), pain (β = 0.13), fatigue (β = 0.24), body image (β = 0.62), and side effects (β = –0.13) were significant predictors of overall QoL while controlling for other predictor variables. Patients who experienced higher levels of disease activity, fatigue severity, pain levels, and greater degree of body dissatisfaction had significantly poorer QoL. Fewer side effects experienced from CLE medications were significantly associated with higher QoL. Conclusions Study findings support the considerable burden associated with CLE. Several modifiable variables such as pain, fatigue, body image, and disease activity were associated with QoL. Therefore, interventions that incorporate these variables may reduce negative impacts on QoL life and improve health outcomes in CLE patients. Furthermore, given the chronic and recurring nature of the condition, strategies focused on improving QoL are needed for this vulnerable population.

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Expression pattern of tissue-resident memory T cells in cutaneous lupus erythematosus

Lupus ◽

10.1177/09612033211017218 ◽

2021 ◽

pp. 096120332110172

Author(s):

Hyeon-Jung Gu ◽

Shinyoung Song ◽

Joo Young Roh ◽

YunJae Jung ◽

Hee Joo Kim

Keyword(s):

T Cells ◽

Lupus Erythematosus ◽

Memory T Cells ◽

Cutaneous Lupus Erythematosus ◽

Discoid Lupus Erythematosus ◽

Type I ◽

Systemic Lupus ◽

Peripheral Tissues ◽

Resident Memory T Cells ◽

Cutaneous Lupus

Background Tissue resident memory T cells (TRMs) persist long-term in peripheral tissues without recirculation, triggering an immediate protective inflammatory state upon the re-recognition of the antigen. Despite evidence incriminating the dysregulation of TRMs in autoimmune diseases, few studies have examined their expression in cutaneous lupus erythematosus (CLE). Objectives We aimed to examine whether there are differences among TRM populations in CLE depending on different clinical conditions, such as the CLE subtype or association with systemic lupus erythematosus, and to determine the effect of type I interferon (IFN) on the development of TRMs in CLE. Methods CLE disease activity was evaluated using the Cutaneous Lupus Erythematosus Disease Area and Severity Index. The expression of the TRM markers CD69 and CD103 in CLE lesions was evaluated by immunofluorescence. Flow cytometry was performed on peripheral blood mononuclear cells after IFNα treatment. Results The number of TRMs expressing either CD69 or CD103 was significantly higher in CLE lesions than in control skin; however, it was not significantly different between discoid lupus erythematosus and subacute CLE, or dependent on the presence of concomitant systemic lupus. Lesional severity was not correlated with an increase in TRMs in CLE. IFNα treatment induced a conspicuous increase in CD69 expression in skin-homing T cells, more profoundly in CD4+ T cells than in CD8+ T cells. Conclusions Skin TRMs, either CD69 or CD103-positive cells, showed increased levels in the lesional skin of CLE, and IFNα increased the expression of CD69 in T cells.

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Atypical and Rare Forms of Cutaneous Lupus Erythematosus: The Importance of the Diagnosis for the Best Management of Patients

Dermatology ◽

10.1159/000515766 ◽

2021 ◽

pp. 1-10

Author(s):

Astrid Herzum ◽

Giulia Gasparini ◽

Emanuele Cozzani ◽

Martina Burlando ◽

Aurora Parodi

Keyword(s):

General Practitioner ◽

Autoimmune Disease ◽

Lupus Erythematosus ◽

Cutaneous Lupus Erythematosus ◽

Cutaneous Manifestations ◽

Skin Manifestation ◽

Systemic Involvement ◽

Best Management ◽

Wide Range ◽

Cutaneous Lupus

Lupus erythematosus (LE) is an autoimmune disease with a wide range of clinical and cutaneous manifestations. Along with the well-known typical cutaneous manifestations of LE, some cutaneous manifestations are rarer, but still characteristic, enabling the dermatologist and the general practitioner who know them to suspect cutaneous LE (CLE) and investigate a possible underlying systemic involvement. Indeed, not infrequently a skin manifestation is the first presentation of systemic LE (SLE), and >75% of SLE patients show signs of skin disease during the course of the illness. Especially, SLE involvement occurs in cases of acute CLE, while it is uncommon in subacute CLE and rare in chronic CLE. This review aims to concentrate especially on atypical cutaneous manifestations of LE to enable the clinician to diagnose even the rarest forms of CLE.

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The value of lymphocytopenia as a marker of systemic involvement in cutaneous lupus erythematosus

British Journal of Dermatology ◽

10.1046/j.1365-2133.2002.04588.x ◽

2002 ◽

Vol 146 (5) ◽

pp. 869-871 ◽

Cited By ~ 13

Author(s):

J. Wenzel ◽

R. Bauer ◽

M. Uerlich ◽

T. Bieber ◽

I. Boehm

Keyword(s):

Lupus Erythematosus ◽

Cutaneous Lupus Erythematosus ◽

Systemic Involvement ◽

Cutaneous Lupus

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Development of a working core outcome set for cutaneous lupus erythematosus: a practical approach to an urgent unmet need

Lupus Science & Medicine ◽

10.1136/lupus-2021-000529 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000529

Author(s):

Lisa N Guo ◽

Lourdes M Perez-Chada ◽

Robert Borucki ◽

Vinod E Nambudiri ◽

Victoria P Werth ◽

...

Keyword(s):

Disease Activity ◽

Outcome Measures ◽

Lupus Erythematosus ◽

Global Assessment ◽

Core Outcome Set ◽

Cutaneous Lupus Erythematosus ◽

Core Outcome ◽

Outcome Set ◽

Starting Point ◽

Cutaneous Lupus

ObjectiveThe lack of standardised outcomes and outcome measures for cutaneous lupus erythematosus (CLE) represents a substantial barrier to clinical trial design, comparative analysis and approval of novel investigative treatments. We aimed to develop a working core outcome set (COS) for CLE randomised controlled trials and longitudinal observational studies.MethodsWe conducted a multistage literature review of CLE and SLE studies to generate candidate domains and outcome measures. Domains were narrowed to a working core domain set. Outcome measures for core domains were identified and examined.ResultsProposed core domains include skin-specific disease activity and damage, investigator global assessment (IGA) of disease activity, symptoms (encompassing itch, pain and photosensitivity), health-related quality of life (HRQoL) and patient global assessment (PtGA) of disease activity. Recommended physician-reported outcome measures include the Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and Cutaneous Lupus Activity IGA (CLA-IGA). For the domains of symptoms, HRQoL and PtGA of disease activity, we were unable to recommend one clearly superior instrument.ConclusionThis work represents a starting point for further refinement pending formal consensus activities and more rigorous evaluations of outcome measure quality. In the interim, the proposed working COS can serve as a much-needed guide for upcoming CLE clinical trials.

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A clinical and epidemiological study on discoid lupus erythematosus

International Journal of Research in Dermatology ◽

10.18203/issn.2455-4529.intjresdermatol20183165 ◽

2018 ◽

Vol 4 (3) ◽

pp. 396 ◽

Cited By ~ 1

Author(s):

Geetharani Gopalan ◽

Sudha R. Gopinath ◽

Kothandaramasamy R. ◽

Sathesh Pandian

Keyword(s):

Lupus Erythematosus ◽

Severe Disease ◽

Disease Onset ◽

Discoid Lupus Erythematosus ◽

Systemic Involvement ◽

Male Ratio ◽

Lupus Panniculitis ◽

Female Predominance ◽

Complete Physical Examination ◽

Cutaneous Lupus

Background: Discoid lupus erythematosus (DLE) is the commonest form of cutaneous lupus erythematosus.The objective of our study is to analyze the clinical and epidemiological aspects of DLE.Methods: All clinically diagnosed cases of DLE attending the dermatology OPD from October 2010 to September 2012were included in the study. A detailed history, complete physical examination, biopsy for confirmation and other relevant investigations were done in all cases.Results: The incidence was 4.79 per 10000 cases (51 of 106368 dermatology patients) showing female to male ratio of 4.1:1. Localized type was more common than the disseminated type. Few lesions (less than five) in a localized area without head and neck involvement were also classified as localized type in this study. Mucosal, verrucous, tumid and lupus panniculitis were the variants of DLE encountered. The sites involved were face, scalp, trunk, upper and lower limb in descending order of frequency. Antinuclear antibody (ANA) was positive in 22 of 30 cases done (73%). The systemic involvement was seen in 15 patients all of whom were diagnosed as systemic lupus erythematosus (SLE). Squamous cell carcinoma was seen in 2 cases of disseminated DLE.Conclusions: Majority of patients had disease onset at 3rd to 5th decade showing female predominance. When compared to localized type, disseminated type was found more frequently in males. Early onset and severe disease was noted among offspring born to a patient suffering from disseminated DLE. Serious morbidity like lupus nephritis was observed only in 1 case. The occurrence of DLE over the herpes zoster scar was an interesting observation.

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